Ready-to-use, stable emulsion

ABSTRACT

The present invention relates to a stable emulsion, ready for use, of fat-soluble vitamins or carotenoids, a process for the preparation thereof, and the use thereof as addition to animal feeds, human foods and dietary supplements, and cosmetic and pharmaceutical compositions.

RELATED APPLICATIONS

This application is a national stage application under 35 U.S.C. §371 ofPCT/EP2009/062768, filed Oct. 1, 2009, and claims priority of Europeanapplication 08165989.8, filed Oct. 7, 2008.

The present invention relates to a stable emulsion, ready for use, offat-soluble vitamins or carotenoids, a process for the preparationthereof, and the use thereof as addition to animal feeds, human foodsand dietary supplements, and cosmetic and pharmaceutical compositions.

The fat-soluble vitamins A, D, E or K, and the derivatives thereof, andthe carotenoids such as, for example, canthaxanthin, astaxanthin,zeaxanthin, lutein, lycopene or β-carotene are often employed notdirectly as pure substances in the animal feed and human foodindustries, the cosmetic industry and the pharmaceutical industry. Onthe contrary, formulations of these fat-soluble substances are used,thus making it possible to disperse the fat-soluble substanceshomogeneously in finely dispersed form in a water-containing medium.Both solid and liquid formulations of these fat-soluble substances areemployed commercially, depending on the area of application.

Whereas vitamins A, D or K are ordinarily employed in the livingorganism, because of their physiological effect, vitamin E is frequentlyalso used as antioxidant in various applications in vitro. Carotenoids,which likewise have an antioxidant effect, are employed as colorants inmany applications and, in this case, can simultaneously fulfill aphysiological function. β-Carotene for example is colorant andprovitamin A.

In the beverage industry, additives are ordinarily added in the form ofliquid concentrates to the beverages. In the case of water-soluble,powdered formulations, normally aqueous dispersions are initiallyprepared from these powders in the production process. In the case ofliquid formulations such as, for example, emulsions, this process stepis unnecessary.

EP 0 239 086 describes emulsions of a carotenoid which is dissolved inoil, where the oil droplets are stabilized by employing a mixture of anester of a long-chain fatty acid with ascorbic acid and a coldwater-soluble starch product such as, for example, starch octenylsuccinate. The carotenoid concentration in these emulsions is between0.1 and 2%.

In EP 0 551 638, stable liquid emulsions of fat-soluble vitamins orcarotenoids are prepared, the continuous phase being glycerol or aglycerol-water mixture, and employing as emulsifier and stabilizer anester of ascorbic acid with long-chain fatty acids. In the case ofβ-carotene, the products are notable for a brilliant yellow hue.

The emulsions, disclosed in the prior art, of fat-soluble activesubstances which comprise the emulsifier ascorbyl palmitate are as yetunsatisfactory for use in mineral-rich sports drinks or on use ofdrinking water with a high content of calcium or magnesium ions, becauseformation of a ring is observed in the beverage bottles, indicatinginstability of the emulsion employed.

The present invention was based on the object of providing a stableemulsion ready for use, which both exhibits good storage stability inrelation to microbiological attack, and is thermally insensitive and inparticular shows improved stability on use in calcium- ormagnesium-containing beverages or on use of drinking water with a highcontent of calcium or magnesium ions.

This object is achieved by a stable emulsion ready for use, comprising

-   a) a dispersed oil phase which comprises a fat-soluble vitamin or a    carotenoid, and-   b) an aqueous phase which comprises a physiologically tolerated    polyalcohol and a chemically modified starch as water-soluble    protective colloid,

in which the content of fat-soluble vitamin or of carotenoid is at least2% by weight, and the content of a further substance with an emulsifyingeffect besides the chemically modified starch is less than 2% by weight,where the % by weight data are in each case based on the total weight ofthe emulsion.

The content of the fat-soluble vitamin or of the carotenoid in thestable emulsion ready for use according to the invention is at least 2%by weight, preferably 3 to 30% by weight, particularly preferably 3 to12% by weight, in particular 3 to 6% by weight, where the % by weightdata are based on the total weight of the emulsion.

The content of a further substance with an emulsifying effect besidesthe chemically modified starch in the stable emulsion ready for useaccording to the invention is less than 2% by weight, preferably lessthan 1% by weight. If the further substance with an emulsifying effectis ascorbyl palmitate, the content of ascorbyl palmitate is preferablyless than 0.5% by weight, particularly preferably less than 0.25% byweight, especially less than 0.1% by weight, where the % by weight dataare based on the total weight of the emulsion.

The fat-soluble vitamin may be for example vitamins A, D, E or K or aderivative thereof. The stable emulsion ready for use according to theinvention preferably comprises a carotenoid such as, for example,canthaxanthin, astaxanthin, zeaxanthin, lutein, lycopene or β-carotene.Preferred carotenoids are lycopene or β-carotene, especially β-carotene.The stable emulsion ready for use according to the invention preferablycomprises a dispersed oil phase which comprises a carotenoid, preferablylycopene or β-carotene, especially β-carotene, dissolved in aphysiologically tolerated oil.

Suitable physiologically tolerated oils are in principle oils ofsynthetic, mineral, vegetable or animal origin. Examples are sesame oil,corn oil, cottonseed oil, soybean oil, peanut oil, esters ofmedium-chain vegetable fatty acids, oleostearin, liquid paraffin,glyceryl stearate, isopropyl myristate, diisopropyl adipate,cetylstearyl 2-ethyl-hexanoate, hydrogenated polyisobutene, caprylicacid/capric acid triglycerides, palm oil, palm kernel oil, lanolin andPUFAs (polyunsaturated fatty acids) such as eicosapentaenoic acid (EPA),docosahexaenoic acid (DHA) and alpha-linolenic acids.

Physiologically tolerated oils of vegetable or animal origin which areliquid at 30° C. are preferred, such as sunflower oil, palm oil, palmkernel oil, sesame oil, corn oil, cottonseed oil, soybean oil, peanutoil, esters of medium-chain triglycerides (so-called MCT oils), fishoils such as mackerel, sprat or salmon oil. Physiologically toleratedoils of vegetable origin which comprise as far as possible onlysaturated fatty acids are particularly preferred, such as, for example,palm kernel oil or coconut oil, especially the esters of medium-chaintriglycerides obtainable therefrom.

The stable emulsion ready for use according to the invention comprisesan aqueous phase which comprises a physiologically tolerated polyalcoholand a chemically modified starch as water-soluble protective colloid.The content of the physiologically tolerated polyalcohol is preferablyfrom 10 to 60% by weight, particularly preferably from 30 to 55% byweight, based on the total weight of the emulsion.

The physiologically tolerated polyalcohol is preferably glycerol,monoesters of glycerol with C₁-C₅ monocarboxylic acids, monoethers ofglycerol or sorbitol. Glycerol is particularly preferred asphysiologically tolerated polyalcohol.

The content of the chemically modified starch in the stable emulsionready for use according to the invention is preferably from 5 to 40% byweight, in particular 10 to 25% by weight, based on the total weight ofthe emulsion.

Chemically modified starch means chemically and/or enzymaticallyprepared starch transformation products. Possibilities in thisconnection are starch ethers, starch esters or starch phosphates.Preferred representatives from this group are starch esters, especiallyoctenyl succinate starch such as, for example, Capsul® (sodiumoctenylsuccinate starch) from National Starch, Cleargum CO 01 from Roquette orPurity® Gum 2000 (sodium octenylsuccinate starch) from National Starch,especially a sodium octenylsuccinate starch such as Purity® Gum 2000.

The content of the dispersed oil phase in the stable emulsion ready foruse according to the invention is preferably from 10 to 40% by weight,in particular 10 to 30% by weight, based on the total weight of theemulsion.

A preferred stable emulsion ready for use according to the invention hasa dispersed oil phase which more than 90% by weight, in particular morethan 95% by weight, consists of a carotenoid and a physiologicallytolerated oil.

To increase the stability of the active substance toward oxidativedegradation it is advantageous for the emulsion to comprise stabilizerssuch as α-tocopherol, t-butylhydroxytoluene, t-butylhydroxyanisole,ascorbic acid or ethoxyquin, especially α-tocopherol.

A particularly preferred stable emulsion ready for use according to theinvention is one where the dispersed oil phase comprises from 3 to 6% byweight of β-carotene and from 7 to 20% by weight of a medium-chaintriglyceride, the aqueous phase comprises from 10 to 25% by weight ofstarch sodium octenyl succinate and from 30 to 55% by weight ofglycerol, and the ascorbyl palmitate content in the emulsion is lessthan 0.5% by weight, preferably less than 0.25% by weight, in particularless than 0.1% by weight, where the % by weight data are based in eachcase on the total weight of the emulsion.

The dispersed oil phase in the stable emulsion ready for use accordingto the invention is present in the form of small oil droplets in thecontinuous aqueous phase. The particle size of the droplets of thedispersed oil phase may generally extend from 100 nm to 100 μm. Thedroplets of the dispersed oil phase preferably have an average particlesize of from 250 to 500 nm.

The statement of the average particle size refers to the volume-weightedaverage diameter (see handbook for Malvern Mastersizer S, MalvernInstruments Ltd., UK), which can be determined by Fraunhoferdiffraction.

Besides the chemically modified starch, it is possible for the stableemulsions ready for use according to the invention to comprise furtherprotective colloids. The following substances are suitable for thispurpose, for example:

ox, pig or fish gelatin, especially acid- or base-degraded gelatin withBloom numbers in the range from 0 to 250, very particularly preferablygelatin A 100, A 200, A 240, B 100 and B 200, and low molecular weight,enzymatically degraded gelatin types with Bloom numbers 0 and molecularweights of from 15 000 to 25 000 D, such as, for example, Collagel A andGelitasol P (from Stoess, Eberbach), and mixtures of these gelatintypes.

Starch, dextrin, pectin, gum arabic (gum acacia), ligninsulfonates,chitosan, poly-styrenesulfonate, alginates, casein, caseinate,methylcellulose, carboxymethyl-cellulose, hydroxypropylcellulose ormixtures of these protective colloids.

Vegetable proteins such as soybean, rice and/or wheat proteins, it beingpossible for these vegetable proteins to be present partly degraded orin undegraded form.

The invention further relates also to a process for preparing a stableemulsion ready for use, comprising

-   a) a dispersed oil phase which comprises a fat-soluble vitamin or a    carotenoid, and-   b) an aqueous phase which comprises a physiologically tolerated    polyalcohol and a chemically modified starch as water-soluble    protective colloid,

in which the content of fat-soluble vitamin or of carotenoid is at least2% by weight, and the content of a further substance with an emulsifyingeffect besides the chemically modified starch is less than 2% by weight,where the % by weight data are in each case based on the total weight ofthe emulsion,

where an oil phase which comprises a fat-soluble vitamin or a carotenoidand an aqueous phase which comprises a physiologically toleratedpolyalcohol and a chemically modified starch as water-soluble protectivecolloid are emulsified together, and subsequently the emulsion ishomogenized under elevated pressure.

Preferred embodiments in relation to the components of the dispersed oilphase and of the aqueous phase, and the amounts thereof used are to befound in the explanations given at the outset.

The stable emulsion ready for use according to the invention isdistinguished inter alia by itself having good storage stability. It ismoreover possible to incorporate the emulsion of the invention withoutdifficulty into calcium- or magnesium-containing sports drinks or intobeverages which comprise drinking water with a high content of calciumor magnesium ions, with the produced beverages exhibiting good stabilityin relation to an unwanted ring formation.

The stable emulsion ready for use according to the invention is suitableinter alia as additive to human food preparations, for example forcoloring food products such as beverages, as composition for producingpharmaceutical and cosmetic preparations, and for the production ofdietary supplement products, for example of multivitamin products in thehuman and animal sectors. The stable emulsion ready for use ispreferably suitable as addition to beverages.

The present invention therefore further also relates to the use of thestable emulsion ready for use according to the invention described aboveas addition to animal feeds, human foods, dietary supplements andcosmetic and pharmaceutical compositions, in particular as addition tobeverages.

The present invention likewise relates to animal feeds, human foods anddietary supplements, in particular a beverage which comprises the stableemulsion ready for use according to the invention.

The invention is explained by the following examples which do not,however, restrict the invention:

EXAMPLES Example 1

145 g of water and 200 g of glycerol were mixed in a 1 l glass beakerand heated to 60° C. 93 g of modified starch (Purity Gum 2000 fromNational Starch) were added to this mixture. The mixture was left toswell at 60° C. for 60 minutes. 65.5 g of β-carotene dispersion(Lucarotin 33 MCT, BASF, 33% by weight of β-carotene) in a 250 mlthree-necked flask were heated in an oil bath heated to 180° C. untilthe β-carotene was completely dissolved. The oil phase was thenintroduced into the aqueous phase while agitating with a tooth-ringeddisperser (Ultra Turrax) at 10 000 rpm. After an emulsifying time of 15minutes, the emulsion was finely emulsified using a high-pressurehomogenizer at 700 bar. A water-dispersible emulsion with 4% by weightof β-carotene was obtained. When dispersed in water, the β-carotene-oildroplets had an average particle size of 275 nm.

I claim:
 1. A stable emulsion ready for use, comprising a) a dispersedoil phase which comprises from 2 to 6% by weight of β-carotenecompletely dissolved in 7 to 20% by weight of a medium-chaintriglyceride and b) an aqueous phase which comprises from 40 to 60% byweight of glycerol and from 10to 25% by weight of starch sodium octenylsuccinate as water-soluble protective colloid, wherein the content of afurther substance with an emulsifying effect besides the starch sodiumoctenyl succinate is less than 2% by weight, and wherein the % by weightdata are in each case based on the total weight of the emulsion.
 2. Thestable emulsion ready for use according to claim 1, where the dispersedoil phase comprises more than 90% by weight of βcarotene and themedium-chain triglyceride based on the total weight of the dispersed oilphase.
 3. The stable emulsion ready for use according to claim 1 whereinthe content of the β-carotene is from 3 to 6% by weight based on thetotal weight of the emulsion, and wherein the stable emulsion comprisesless than 0.5% by weight of ascorbyl palmitate based on the total weightof the emulsion.
 4. The stable emulsion ready for use according to claim1, wherein the dispersed oil phase is in form of oil droplets having anaverage particle size of from 250 to 500 nm.
 5. A process for preparinga stable emulsion ready for use according to claim 1, comprising: a)mixing glycerol and water and adding the starch sodium octenyl succinateto the mixture of glycerol and water to form the aqueous phase, b)dissolving βcarotene in the medium-chain triglyceride by heating to formthe dispersed oil phase, and c) introducing the dispersed oil phase tothe aqueous phase, emulsifying the dispersed oil phase and the aqueousphase together to obtain an emulsion and subsequently homogenizing theemulsion.
 6. A cosmetic or pharmaceutical composition comprising thestable emulsion ready for use according to claim
 1. 7. An animal feed,human food or dietary supplement comprising the stable emulsion readyfor use according to claim
 1. 8. A beverage comprising the stableemulsion ready for use according to claim 1.